Clinical and environmental isolates of Burkholderia cepacia exhibit differential cytotoxicity towards macrophages and mast cells

Burkholderia cepacia is an emerging opportunistic pathogen that causes fata l infections in patients suffering from cystic fibrosis (CF) and chronic gr anulomatous disease. Various environmental isolates of B. cepacia are, howe ver, capable of degrading environmental pollutants, such as trichloroethyle ne, 2,4,5-trichlorophenoxyacetic acid (2,4,5-T), etc., and are also highly effective in controlling plant diseases caused by nematodes and fungi. Such strains have therefore been proposed for environmental release to clean up toxic dump sites or as biopesticides. Various efforts to distinguish betwe en clinical and environmental isolates of B. cepacia with regard to their v irulence characteristics have produced ambiguous results, suggesting that n ewer methods are needed to test for the presence or absence of pathogenic p otential in B. cepacia strains proposed for environmental release. We now r eport that several clinical strains of B. cepacia secrete cytotoxic factors that allow macrophage and mast cell death in the presence of external ATP. Several environmental strains had reduced activity in this regard. We also demonstrate that, while all the strains secrete enzymes that have nucleosi de diphosphate kinase (Ndk), adenylate kinase (Ak) and 5'-nucleotidase acti vity, the level of secretion of the 5'-nucleotidase (and/or ATPase/phosphat ase) appears to be lower in the environmental strains than in the clinical strains. The secretion of these enzymes is specifically activated in the pr esence of eukaryotic proteins such as alpha 2-macroglobulin. As macrophage- or mast cell surface-associated P2Z receptors promote their cell death in the presence of mM concentrations of ATP, and as the secreted ATP-using enz ymes generate various phosphorylated or non-phosphorylated adenine nucleoti des that may even be better agonists than ATP in activating the P2Z recepto rs or may act through the activation of additional purinergic receptors, su ch enzymes may play an important role in allowing B. cepacia to evade host defence.